Reviewed, UniProtKB/Swiss-Prot P58913 (CXD6A_CONPU)

Names and origin

Protein names	Recommended name:     Delta-conotoxin PVIA Alternative name(s):     Lockjaw peptide
Organism	Conus purpurascens (Purple cone)
Taxonomic identifier	41690 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Mollusca › Gastropoda › Orthogastropoda › Apogastropoda › Caenogastropoda › Sorbeoconcha › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	81 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Delta-conotoxins bind to site 6 of voltage-gated sodium channels and inhibit the inactivation process. In mice, injection of this toxin causes hyperactivity, rapid running, limb extension, and death. In fish, the peptide elicites spurts of rapid swimming, with twisted motions, quivering fins and the lockjaw extended mouth syndrome. Rigid paralysis and death are observed at higher doses. In mollusks, this peptide is inactive. Injection of this peptide together with the kappa-conotoxin PVIIA causes the sudden tetanus of prey (STOP) syndrome, which is a single, lethal "fin-pop" in envenomated fish.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom duct.
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin By similarity.
Post-translational modification	The difference between delta-conotoxin PVIA and [deamido]-delta-conotoxin PVIA lies in the state of amidation of Gly-80.
Sequence similarities	Belongs to the conotoxin O superfamily. Delta-type family.
Mass spectrometry	Molecular mass is 2997.3 Da from positions 52 - 80. Ref.1

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin Signal
Molecular function	Ionic channel inhibitor Neurotoxin Sodium channel inhibitor Toxin
PTM	Amidation Cleavage on pair of basic residues Disulfide bond Hydroxylation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	sodium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Propeptide	23 – 49	27	By similarity		PRO_0000034898
	Peptide	52 – 80	29	Delta-conotoxin PVIA Ref.1 Ref.2		PRO_0000034899
Amino acid modifications
	Modified residue	57	1	4-hydroxyproline Ref.1
	Modified residue	65	1	4-hydroxyproline Ref.1
	Modified residue	80	1	Glycine amide; in form delta-conotoxin PVIA
	Disulfide bond	54 ↔ 69		By similarity
	Disulfide bond	61 ↔ 73		By similarity
	Disulfide bond	68 ↔ 78		By similarity
Experimental info
	Mutagenesis	59	1	T → A: No loss of activity. Ref.3
	Mutagenesis	60	1	F → A: Loss of biological activity. However, coinjection of this mutant protects against the wild-type conotoxin, suggesting that the mutant binds competitively to the wild-type conotoxin ligand site. Such a protective effect does not occur for all physiological targets. Ref.3
	Mutagenesis	63	1	I → A: Loss of activity. Ref.3
	Mutagenesis	64	1	K → A: No loss of activity. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P58913-1 [UniParc]. Last modified July 26, 2002. Version 1. Checksum: ACCFE9E1C65ABFEC	FASTA	81	8,945
	10 20 30 40 50 60 MKLTCVMIVA VLFLTAWTFV TADDSKNGLE NHFWKARDEM KNREASKLDK KEACYAPGTF 70 80 CGIKPGLCCS EFCLPGVCFG G

References

[1]	"Purification, characterization, synthesis, and cloning of the lockjaw peptide from Conus purpurascens venom." Shon K.-J., Grilley M.M., Marsh M., Yoshikami D., Hall A.R., Kurz B., Gray W.R., Imperial J.S., Hillyard D.R., Olivera B.M. Biochemistry 34:4913-4918(1995) [PubMed: 7711013] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 52-80, SYNTHESIS OF 52-80, HYDROXYLATION AT PRO-57 AND PRO-65, MASS SPECTROMETRY. Tissue: Venom and Venom duct.
[2]	"Strategy for rapid immobilization of prey by a fish-hunting marine snail." Terlau H., Shon K.-J., Grilley M.M., Stocker M., Stuehmer W., Olivera B.M. Nature 381:148-151(1996) [PubMed: 12074021] [Abstract] Cited for: PROTEIN SEQUENCE OF 52-80, SYNTHESIS OF 52-80.
[3]	"Delta-conotoxin structure/function through a cladistic analysis." Bulaj G., DeLaCruz R., Azimi-Zonooz A., West P., Watkins M., Yoshikami D., Olivera B.M. Biochemistry 40:13201-13208(2001) [PubMed: 11683628] [Abstract] Cited for: SYNTHESIS OF 52-80, MUTAGENESIS OF THR-59; PHE-60; ILE-63 AND LYS-64.

Cross-references

Sequence databases
PIR	A58651.
3D structure databases
ModBase	Search...
Family and domain databases
InterPro	IPR004214. Conotoxin. IPR012322. Conotoxin_d-typ_CS. [Graphical view]
Pfam	PF02950. Conotoxin. 1 hit. [Graphical view]
PROSITE	PS60005. DELTA_CONOTOXIN. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

CXD6A_CONPU

Accession

Primary (citable) accession number: P58913

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 26, 2002
Last sequence update:	July 26, 2002
Last modified:	June 16, 2009
This is version 46 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Tox-Prot (Toxin Annotation Project)